DESCRIPTION: (provided by the applicant) My lab is interested in studying the molecular mechanisms and neuronal circuitry that mediate distinct orofacial pain, using the mouse as a model system. In the craniofacial region, pain transmission is mediated by the trigeminal sensory neurons that innervate diverse tissue on the entire face. Interestingly, the perceived pain originated from different areas is different. For example, the pain of a headache is usually very different from dental pain. Furthermore, different craniofacial regions tend to be associated with or develop distinct chronic pains. We hypothesize that the three trigeminal divisions innervating different targets should express distinct molecular programs and engage in distinct neural circuits, thus enabling them to mediate different orofacial pain. In Specific Aim 1, we will identify the molecular differences among the separate divisions of trigeminal ganglion using genomic approaches. The goal is to generate comprehensive lists of molecular signatures for neurons innervating distinct head/face regions and answer the question: "How heterogeneous are nociceptive trigeminal neurons". In Specific Aim 2, we will use some of the molecular markers that we already identified to genetically map the neuronal projections from specific trigeminal populations and study the nociceptive sensory maps in normal mice and in mice with experimentally induced chronic pain. These studies should allow us to address two fundamental questions in pain research: (1) Do different trigeminal neurons form convergent projections at certain locations in the hindbrain? (2) Is abnormal axon sprouting the structural basis for chronic pain? Finally, in Specific Aim 3, we will test the functions of two of the maxillomandibular expressed transcription factors to prove, in principle, that genes specifically present in some but not all trigeminal divisions are important for either their specialized development requirements or their specific functions.